**4. Risk assessment of morbillivirus infection based on SLAM interface structures**

Host-Virus Specificity of the Morbillivirus Receptor, SLAM, in Marine Mammals:

Morbillivirus, a member of the family Paramyxoviridae, is a causative agent of mass mortalities of marine mammals. To date, four virus species, MV, RPV, PPRV, and CDV have been identified in land mammals, and two virus species, PDV and CMV, have been identified in seals and cetaceans, respectively [4,47]. The notable biological feature of morbillivirus is its high level of host specificity. The cellular receptor for a virus is a major determinant of its host specificity and tissue tropism. SLAM is the principal cellular receptor for morbilliviruses allowing entry and propagation [18,19]. SLAM contains two immunoglobulin-like domains, the V and C2 domains, in the extracellular region. The morbillivirus H protein binds to the V domain on the target cells, which triggers viral infection [53] To assess the host–virus specificity of morbillivirus in marine mammals, we determined the complete nucleotide sequences of SLAM from five species belonging to cetaceans, pinippeds, and sirenians, and generated 3D homology models. The results showed that the overall structures are similar in the mammals examined. We found 32 amino acid residues on the interface of SLAM V domain that are potentially involved in the interaction with viruses. Among them, a set of 18 amino acid residues is important for morbillivirus binding because some residues in the set differ among the mammal groups, which are susceptible to different morbillivirus species. A change in some residues in the set may cause an electrostatic change on the interface surface. These amino acid residues are

Analysis of these residues on the interfaces of SLAMs will be useful to assess the risk of morbillivirus infection in wild animals. Recent climate change may increase the opportunities for new contacts among wild mammals and for the transmission of viruses. In the present study, we propose a new approach to assess the viral sensitivities of wild mammals by analyzing the host receptors. This approach will contribute to the conservation

The authors are grateful for the cooperation of the Yokohama Hakkeijima Sea-Paradise Aquamuseum (Yokohama), Kamogawa Sea World (Chiba), Churaumi Aquarium

*Japan Agency for Marine-Earth Science and Technology (JAMSTEC), Yokosuka, Japan* 

*Protein Research Unit, National Institute of Agrobiological Science, Tsukuba, Japan* 

**5. Conclusion** 

**Author details** 

Kazue Ohishi\*

Rintaro Suzuki

 \*

**Acknowledgement** 

Corresponding Author

thought to be important for host–virus specificity.

of wildlife including marine mammals and ecosystems.

and Tadashi Maruyama

(Okinawa), and Kanazawa Zoo (Yokohama).

Risk Assessment of Infection Based on Three-Dimensional Models 197

Human beings have a long history of diseases caused by morbilliviruses, which introduced devastating contagious diseases to humans and domestic animals. Since Jenner's seminal discovery of the concept of immunity and vaccines, vaccines against various pathogens have been developed. By virtue of that great endeavor, an effective vaccine against measles is now available [79,80]. It has reduced measles deaths worldwide by 74% between 2000 and 2010 (from 535,300 to 139,300), although measles is still a threat for children in developing countries [81]. Rinderpest induced by RPV, one of the oldest recorded livestock plagues, has been actually eradicated by the success of the Global Rinderpest Eradication Programme [82-84]. Thus, numerous efforts at eradication have achieved the control of human and domesticated animal diseases. Similar control of morbillivirus infections in wild animals will be one of the most important issues in the field of veterinary medicine in the 21st century. Marine mammals have large geographical ranges in the oceans. For example, baleen whales are known to migrate seasonally from the equator to the polar seas, indicating that they may be a dynamic vector for infectious diseases. In addition, recent global climate change may alter the ecology of marine mammals, such as their habitats, migration patterns, food, and behavior, and may increase opportunities for contact among previously geographically separate mammalian populations. These alterations may increase the possibility of viral transmission and the likelihood of outbreaks in susceptible mammalian populations.

In viral infection, disease incidence, and transmission, several factors in host cells play a key role. In addition, ecological factors such as animal distribution, population structure and size, and behavior are decisive factors in actual infection. In the present study, we used a new approach to assess the potential infectivity of morbilliviruses based on receptor structure predictions. The residues on the interface of the SLAM V domain probably contribute to virus binding, and some residues among them are key for host–virus specificities. The analysis of these residues on 3D models of the SLAM receptor is useful for estimating the risk of morbillivirus infection in wild animals. This approach is applicable to animals for which no information on infection and disease. For the animals, it is possible to predict potential infection with known morbilliviruses. This may reveal possible infection spectra of morbilliviruses and suggest which mammals are reservoirs that maintain the viruses and how these viruses spread among wild mammals in nature.

Control of infectious diseases in wild animals is very difficult. However, even though we cannot stop outbreaks from occurring in nature, information on the potential sensitivity of wild mammals against a virus may minimize the damage or prevent the spread of disease by such means as artificial transportation. Because marine mammals are positioned at the top of oceanic food chain, a decrease in marine mammal populations will affect marine ecosystems. We believe that the present study contributes to the conservation of marine mammals and their ecosystems.
